title: Inhibitory effect of omeprazole on the metabolism of midazolam in vitro.
abstract: To examine the effect of omeprazole on the hepatic drug metabolizing enzyme system microsomes from rat and human liver samples were incubated with midazolam (CAS 59467-70-8) in the absence and presence of various concentrations of omeprazole (CAS 73590-58-6), its sulfone metabolite and for comparison also with cimetidine. In the extracted incubation mixtures unchanged midazolam, a-OH-midazolam, 4-OH-midazolam and di-OH-midazolam were analyzed by HPLC. In both species omeprazole (and its sulfone) inhibited the formation of all three oxidized metabolites of midazolam and the corresponding IC50-values (range 0.2-1.3 mmol/l for rat microsomes and 0.2-1.5 mmol/l for human microsomes) were comparable to cimetidine (range 0.05 to 3.8 mmol/l). These results indicate that the oxidative metabolism of midazolam can be inhibited in vitro by omeprazole (and/or its sulfone metabolite) and this interaction should be considered if both drugs are administered concomitantly in man.
authors.affiliation: Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Fed. Rep. of Germany.
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: U
authors.initials: U
authors.lastname: Klotz
mesh_terms: D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D008874:Midazolam / Q000378:metabolism*; D009853:Omeprazole / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
chemical_list: D009853:Omeprazole; D008874:Midazolam